Liver macrophages inhibit the endogenous antioxidant response in obesity-associated insulin resistance

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dc.contributor.authorAzzimato, Valerioen
dc.contributor.authorJager, Jenniferen
dc.contributor.authorChen, Pingen
dc.contributor.authorMorgantini, Ceciliaen
dc.contributor.authorLevi, Lauraen
dc.contributor.authorBarreby, Emelieen
dc.contributor.authorSulen, Andreen
dc.contributor.authorOses, Carolinaen
dc.contributor.authorWillerbrords, Joosten
dc.contributor.authorXu, Connieen
dc.contributor.authorLi, Xidanen
dc.contributor.authorShen, Joanne X.en
dc.contributor.authorAkbar, Naveeden
dc.contributor.authorHaag, Larsen
dc.contributor.authorEllis, Ewaen
dc.contributor.authorWålhen, Kerstinen
dc.contributor.authorNäslund, Eriken
dc.contributor.authorThorell, Andersen
dc.contributor.authorChoudhury, Robin P.en
dc.contributor.authorLauschke, Volker M.en
dc.contributor.authorRydén, Mikaelen
dc.contributor.authorCraige, Siobhan M.en
dc.contributor.authorAouadi, Myriamen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2021-01-12T13:32:09Zen
dc.date.available2021-01-12T13:32:09Zen
dc.date.issued2020-02-26en
dc.date.updated2021-01-12T13:31:56Zen
dc.description.abstractObesity and insulin resistance are risk factors for nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. Because no approved medication nor an accurate and noninvasive diagnosis is currently available for NAFLD, there is a clear need to better understand the link between obesity and NAFLD. Lipid accumulation during obesity is known to be associated with oxidative stress and inflammatory activation of liver macrophages (LMs). However, we show that although LMs do not become proinflammatory during obesity, they display signs of oxidative stress. In livers of both humans and mice, antioxidant nuclear factor erythroid 2– related factor 2 (NRF2) was down-regulated with obesity and insulin resistance, yielding an impaired response to lipid accumulation. At the molecular level, a microRNA-targeting NRF2 protein, miR-144, was elevated in the livers of obese insulin-resistant humans and mice, and specific silencing of miR-144 in murine and human LMs was sufficient to restore NRF2 protein expression and the antioxidant response. These results highlight the pathological role of LMs and their therapeutic potential to restore the impaired endogenous antioxidant response in obesity-associated NAFLD.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/10919/101849en
dc.language.isoenen
dc.rightsIn Copyright (InC)en
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject06 Biological Sciencesen
dc.subject11 Medical and Health Sciencesen
dc.titleLiver macrophages inhibit the endogenous antioxidant response in obesity-associated insulin resistanceen
dc.title.serialScience Translational Medicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Human Nutrition, Foods, & Exerciseen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Techen

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